Intrinsic Cardiac Neurons Research Articles

Modulation of in situ canine intrinsic cardiac neuronal activity by locally applied adenosine, ATP, or analogues

To determine whether adenosine or ATP can modify mammalian intrinsic cardiac neurons, these substances, as well as their analogues 5'-(N-ethylcarboxamido)-adenosine (NECA), N6-cyclopentyladenosine (CPA), and beta,gamma-methylene ATP (beta,gamma-mATP), were applied in microliter quantities adjacent to spontaneously active canine atrial ganglionated plexus neurons in 14 anesthetized open-chest dogs. Adenosine, NECA, and CPA induced neuronal responses, neuronal activity being either increased or decreased in 81, 86, and 86% of the sites tested, respectively. Cardiovascular responses were elicited by these agents in 21-31% of neurally active loci. ATP and beta,gamma-mATP elicited neuronal responses in 100 and 70% of tested loci, respectively. Associated cardiovascular responses were elicited by ATP and beta,gamma-mATP in 35 and 18% of the sites, respectively. After acute decentralization of the intrinsic cardiac nervous system, neuronal responses were elicited by purines in 73% of the previously active sites, while cardiovascular responses were either attenuated or eliminated. It is concluded that exogenous purine nucleosides and nucleotides can modulate the activity generated by in situ intrinsic cardiac neurons presumably by acting on P1 and P2 purinoreceptors. Furthermore, these data indicate that purine sensitive intrinsic cardiac neurons are involved in cardiac regulation.

Modulation of in situ canine intrinsic cardiac neuronal activity by nicotinic, muscarinic, and beta-adrenergic agonists

To investigate whether microvolumes (< or = 10 microliters) of nicotinic, muscarinic, and beta-adrenergic agonists can modify intrinsic cardiac neuronal activity, nicotine, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), bethanechol chloride, and isoproterenol were separately administered adjacent to spontaneously active in situ epicardial neurons in 15 anesthetized dogs. Neuronal activity generated by 46 of 63 neurons was modified by these neurochemicals, with about half of the neurons affected by more than one agent. In association with these neuronal responses, cardiodynamic responses were elicited in 17 instances. When cardiac augmentation was elicited, it persisted after the administration of atropine but not of timolol. After cardiac decentralization, 40% of previously active neurons were still modified by local application of chemicals; cardiodynamic responses were elicited in nine instances. The activity of six units was modified by isoproterenol after subsequent administration of hexamethonium. These data confirm that intrinsic cardiac neurons possess nicotinic and muscarinic receptors and demonstrate that some intrinsic cardiac neurons also possess beta-adrenergic receptors. Furthermore, these data demonstrate that intrinsic cardiac neurons with nicotinic, muscarinic, and beta-adrenergic receptors are involved in cardiac regulation.

Cocultures of adult ventricular myocytes with stellate ganglia or intrinsic cardiac neurones from guinea pigs: spontaneous activity and pharmacological properties.

The aim was to develop long term primary cocultures of adult ventricular myocytes with autonomic neurones dissociated from stellate or intrinsic cardiac ganglia. This was to provide an experimental model for the investigation of the regulatory role of autonomic neurones with respect to cardiac myocyte function. Ventricular myocytes and stellate and intrinsic cardiac neurones were enzymatically dissociated from adult male guinea pigs and plated together on 13 mm cover slips; the cultures were maintained in an incubator for two to 10 weeks. The electrical properties of cultured myocytes and neurones were investigated by means of a conventional microelectrode technique and the spontaneous contractile activity of the myocytes was recorded by a video system. The electrical, contractile, and pharmacological properties of myocyte-neuronal networks were investigated by superfusing the cultures with various neuromodulators and blockers. The electrical properties of the cultured myocytes and neurones were similar to those reported in other in vitro studies. Innervated and non-innervated cardiomyocyte cultures responded differently, however, to various pharmacological interventions. Spontaneous contractions were attenuated by tetrodotoxin (4 x 10(-7) M), beta adrenergic blockade, and nicotinic blockade more in cocultures than in cardiac myocyte cultures alone. On the other hand, the beta agonist isoproterenol increased the spontaneous beating in both types of cocultures more than in myocytes alone. The effects of the muscarinic agonist bethanechol and the muscarinic blocker atropine were not significantly different in innervated and non-innervated cultures. Nicotine induced either an increase or decrease in contractile rates of both cocultures and did not affect non-innervated myocyte cultures. Cocultures of myocytes and autonomic neurones alter the responses of myocytes relative to cultures without neurones. The results suggest that functional contacts can be established between adult myocytes and dissociated neurones in primary cultures. Contractile rates of such myocyte cultures are influenced by the presence of neurones. Neurones innervating these cultures were modified by beta adrenergic, muscarinic, and nicotinic agents.

Amino acids modify activity of canine intrinsic cardiac neurons involved in cardiac regulation

The effects of amino acids on intrinsic cardiac neuronal activity identified in 10 anesthetized dogs were investigated. Local injection of small volumes (1-10 microliters) of the excitatory amino acids, glutamate (100 mM) and aspartate (10 mM), and the inhibitory amino acids, gamma-aminobutyric acid (GABA; 10 mM) and glycine (10 mM), modified the activity of 39 of 50 identified neurons. Spontaneous activity of eight neurons was modified by both excitatory and inhibitory amino acids. Cardiodynamic responses accompanied neuronal activity modification in 15 instances. After acute decentralization, repeat doses of amino acids altered the activity of 21 neurons and elicited cardiovascular responses in 7 instances. Neuronal and cardiovascular responses were elicited after atropine administration. Neuronal but not cardiac responses were elicited after subsequent timolol administration. In other animals, GABA but not other amino acids elicited neuronal and cardiodynamic responses after hexamethonium administration in decentralized preparations, indicating that non-nicotinic synapses were involved in some GABA-induced responses. These results demonstrate that excitatory and inhibitory amino acids can modify intrinsic cardiac neuronal activity such that, as a consequence, cardiac variables can be modified.

Peptidergic modulation of in situ canine intrinsic cardiac neurons

In order to determine which peptides are involved in modulating intrinsic cardiac neurons, angiotensin II, atrial natriuretic peptide, bradykinin, calcitonin gene-related peptide, enkephalin, neuropeptide Y, oxytocin, substance P, and vasoactive intestinal peptide dissolved in saline were administered individually by microinjection adjacent to spontaneously active canine intrinsic cardiac neurons. No neuronal or cardiac responses were elicited when saline was administered into active loci or when peptides were administered into loci with no spontaneous activity. Each peptide elecited neuronal responses when administered into active loci in most animals, bradykinin eliciting neuronal responses in every active locus studied. Concomitant cardiovascular responses were elicited in many cases when every peptide except atriopeptin was studied. After cardiac decentralization, neuronal and cardiovascular responses to repeat doses of peptides occurred with less frequency than before decentralization, implying that connections with central and other intrathoracic neurons can influence the function of peptide-sensitive intrinsic cardiac neurons. After atropine and timolol administration, cardiovascular, but not neuronal, responses to peptides were eliminated, indicating that cardiovascular responses were dependent upon efferent parasympathetic and sympathetic neurons. It is concluded that a number of neuropeptides may be involved in regulation of cardiac function by intrinsic cardiac neurons.

Effects of transient coronary artery occlusion on canine intrinsic cardiac neuronal activity.

In order to further elucidate the regulatory function of canine epicardial neurons, the effects of transient coronary artery occlusion on their spontaneous activity was studied. Fifty-eight individual, spontaneously active units were identified by means of their action potential configurations in specific loci of atrial and ventricular epicardial fat of 10 anesthetized dogs. The activity of 49 of the units was modified by one minute of coronary artery occlusion. Twenty-four of the 49 responding units exhibited increased activity and 37 decreased activity during coronary artery occlusions. Activity changes were sometimes, but not always, associated with decreased left ventricular intramyocardial systolic pressure. During reperfusion, the activity of 6 units was increased compared to control levels, even though ventricular pressures remained the same. Following acute decentralization, 48% of previously active units generated spontaneous activity; the activity of 89% of these was altered during coronary artery occlusion despite the fact that overall cardiodynamics were unchanged. Following hexamethonium administration, the activity generated by 9 of 10 spontaneously active units was modified by coronary artery occlusion. It is concluded that transient coronary artery occlusion can modify the activity generated by intrinsic cardiac neurons, such modification involving central and peripheral neuronal interactions.

Intrinsic Cardiac Neurons

Intrinsic Cardiac Neurons. Physiological evidence indicates that afferent neurons, local circuit neurons, as well as efferent sympathetic and efferent parasympathetic neurons, are located in the mammalian intrinsic cardiac nervous system. Complex interneuronal interactions can occur between these neurons, as well as between such neurons and other intrathoracic and central nervous system neurons. A variety of neurochemicals have been proposed to be involved in such interneuronal interactions. Thus the electrophysiologic properties and synaptology of intrinsic cardiac neurons may be more varied than has been appreciated accounting, at least in part, for the variety of neuronal responses that in situ intrinsic cardiac neurons are capable of displaying. The various interactions that occur between intrinsic cardiac neurons and other intrathoracic neurons, as well as between neurons in all intrathoracic ganglia and the central nervous system, will have to be characterized in order to clarify the role of the autonomic nervous system regulating the heart throughout each cardiac cycle.

Cardiac responses elicited by peptides administered to canine intrinsic cardiac neurons

In order to study the effects of peptides on intrinsic cardiac neurons, substance P, bradykinin, oxytocin, calcitonin gene related peptide, atrial natriuretic peptide and vasoactive intestinal peptide were administered into canine atrial or ventricular ganglionated plexi. When substance P was injected into right atrial or cranial medial ventricular ganglionated plexi heart rate, atrial force and ventricular intramyocardial pressures were augmented. No cardiac changes occurred when similar volumes of saline (i.e., peptide vehicle) were injected into these ganglionated plexi. When bradykinin was injected into atrial or ventricular ganglionated plexi heart rate, atrial force and ventricular force were augmented in ∼50% and depressor responses were elicited in ∼50% of these animals. When oxytocin was injected into right atrial ventral ganglionated plexi heart rate and atrial forces were reduced in five of ten dogs studied. No cardiac changes occurred when oxytocin was injected into left atrial or ventricular ganglionated plexi. No responses were elicited when calcitonin gene related peptide, atrial natriuretic peptide or vasoactive intestinal peptide was administered into atrial or ventricular ganglionated plexi. Following acute decentralization of the heart, no significant responses were elicited by repeat administrations of substance P, bradykinin or oxytocin, implying that connectivity with central nervous system neurons was necessary for consistent responses to be elicited. It is concluded that substance P, bradykinin and oxytocin can affect neurons on the heart such that cardiodynamics are modified, these different peptides eliciting different cardiac responses.

Arrhythmias induced by local cardiac nerve stimulation.

Arrhythmias induced by local cardiac nerve stimulation.

Studies of cardio-regulation in the cockroach, Periplaneta americana.

ABSTRACT The heart of Periplaneta americana is segmentally innervated from the central nervous system by three types of neurone. Two of these types of neurones are neurosecretory; one type contains large granules, the other small granules. The segmental nerves are paired structures which join paired lateral cardiac nerve cords. Both types of neurosecretory neurone liberate their contents in the lateral cardiac nerve cords. The neurones with the small granules also synapse with the myocardium as well as with intrinsic cardiac neurones in the lateral cardiac nerve cords. The third type of neurone from the central nervous system is an ordinary efferent neurone and it synapses with the cardiac ganglion cells. A heart chamber is associated with about six cardiac ganglion cells, three on either side. These send processes up and down the lateral cardiac nerve cord and make synaptic contact with the myocardium. The myocardium is multiterminally and polyneuronally innervated, and electrical coupling between muscle fibres appears to be the rule. The fibres are spontaneously active and generate spike-like electrically excited responses. The timing of the electrically excited responses is influenced by the input from the cardiac ganglion cells which evoke a burst of synaptic potentials during diastole. Control of the cockroach heart appears to be organized on three levels. The basic rhythm is myogenic. The timing of the contractions is influenced by inputs from the intrinsic cardiac ganglion cells possibly via a feedback mechanism involving the contractions of the heart muscle. Finally, the activities of the heart muscle and the cardiac ganglion cells are influenced by inputs from the central nervous system.